Dynamics of the Anti-factor VIII Antibody Signature During Treatment With Emicizumab

Recruiting

• Conditions: Severe Hemophilia A With Inhibitor; Severe Hemophilia A; Severe Hemophilia A Without Inhibitor
• Interventions: Other: no interventions

• Registration Number: NCT05802836
• Lead Sponsor: Christoph Königs

Brief Summary

The goal of this observational study is to learn about the changes of antibodies and inhibitors against the coagulation factor VIII in patients with severe hemophilia A receiving emicizumab therapy. No additional visits or procedures are planned. Patients in this study will continue to receive their routine care and analysis will be done from left over samples from routine visits.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-03-06
• Study First Submitted QC: 2023-04-04
• Study First Posted: 2023-04-07
• Study Start: 2023-04-26
• Status Verified: 2023-07
• Last Update Submitted: 2023-07-07
• Last Update Posted: 2023-07-10
• Primary Completion: 2028-12
• Study Completion: 2029-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Severe congenital hemophilia A (CHA)
• Treatment with emicizumab irrespective of any other treatment
• Informed consent

Exclusion Criteria

• No therapy with emicizumab
• Immunosuppressive therapy
• HIV-infection with CD4 (cluster of differentiation 4) cells <200/µl

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Inhibitor positive, no FVIII therapy	no interventions	Patients with severe hemophilia A receiving emicizumab therapy which are positive for factor VIII Inhibitor and are receiving no factor VIII therapy
Inhibitor positive, FVIII therapy regularly (ITI)	no interventions	Patients with severe hemophilia A receiving emicizumab therapy which are positive for factor VIII Inhibitor and are receiving regularly factor VIII therapy (ITI)
Inhibitor negative, FVIII on demand or regularly	no interventions	Patients with severe hemophilia A receiving emicizumab therapy which are negative for factor VIII Inhibitor (including patients post ITI) and are receiving factor VIII therapy either on demand or regularly,

Primary Outcome Measures

Name	Time	Method
FVIII inhibitor development in inhibitor negative subjects	3 years	Rate of FVIII inhibitor development during three years of emicizumab prophylaxis in inhibitor negative subjects. Assessed with Bethesda Assay (BU/ml). Number of patients who develop an FVIII inhibitor within the study period, but were FVIII inhibitor negative at start of the study.
FVIII antibody development in inhibitor negative subjects	3 years	Rate of FVIII antibody development during three years of emicizumab prophylaxis in inhibitor negative subjects. FVIII anti drug antibody (ADA) is assessed by FVIII specific ELISA (OD=Optical Density). Number of patients who develop an FVIII antibody (ADA) within the study period, but were FVIII inhibitor negative at start of the study.
FVIII inhibitor disappearance in inhibitor positive subjects	3 years	Rate of FVIII inhibitor disappearance during three years of emicizumab prophylaxis in inhibitor positive subjects. Assessed with Bethesda Assay (BU/ml). Number of patients who loose an FVIII inhibitor within the study period, but were FVIII inhibitor positive at start of the study.
FVIII antibody disappearance in inhibitor positive subjects	3 years	Rate of FVIII antibody disappearance during three years of emicizumab prophylaxis in inhibitor positive subjects. FVIII anti drug antibody (ADA) is assessed by FVIII specific ELISA (OD=Optical Density). Number of patients who develop an FVIII antibody within the study period, but were FVIII inhibitor positive at start of the study.

Secondary Outcome Measures

Name	Time	Method
Anti-FVIII antibody development	3 years	Anti-FVIII antibody development (median arbitrary units, OD) over time. Description of antibody development in the different patient groups within the study period.
Quality of the antibody response (FVIII epitopes)	3 years	Description of the location of FVIII epitopes over time, assessed by epitope mapping technique (ELISA)
Response to treatment	3 years	Classification of bleeds as Effective, Partially Effective, Ineffective. Defined as: Effective: Bleeding episode responded to the usual number of injections or dose of FVIII as expected by the treating physician; Partially Effective: The bleeding episode responded with a higher number of injections and/or dose as expected by the treating physician; Ineffective: Routine failure to control hemostasis or hemostatic control required additional agents
Quality of the antibody response (IgG subclasses)	3 years	Description of a potential immune response over time, assessed by IgG subclass determination (ELISA).
Anti-FVIII inhibitor development	3 years	Anti-FVIII inhibitor development (median BU/ml) over time. Assessed with Bethesda Assay (BU/ml). Description of inhibitor development in the different patient groups within the study period. Cut off is 0,6 BU/ml.
Treatment of bleeds	3 years	Description of the use of FVIII and/or Bypassing agents treatment in addition to Emicizumab treatment in case of bleeds.
Time to negative inhibitor titers	3 years	Time to negative inhibitor titers. Assessed with Bethesda Assay (BU/ml). Description of the Time (days) observed for FVIII inhibitor disappearance within the study period in the patient groups. Cut off for inhibitor titer is 0,6 BU/ml.

Trial Locations

Locations (1)

University Hospital Frankfurt, Goethe University; 🇩🇪 Frankfurt, Hessen, Germany